There are a number of illnesses and conditions with unknown etiology, such as atypical connective tissue diseases (e.g., fibromyalgia, chronic fatigue syndrome, and the symptoms associated with exposure to silicone breast implants), and Gulf War Syndrome (GWS), which currently are the focus of considerable research to determine causative agents and treatments. GWS is a blanket term for the illnesses afflicting men and women who served in the Persian Gulf military conflict during 1990-1991 remain ill-defined. GWS is characterized by a variety of symptoms including fatigue, rashes, headaches, arthralgias, myalgias, diarrhea, memory loss, autoimmune thyroid disease, increased allergies and sensitivities to environmental elements, and neurological abnormalities (Grady, et al. Arch. Int. Med., 1998, 158: 367-371; Persian Gulf Veterans Coordinating Board. Arch. Int. Med., 1995, 155: 262-268; Haley, et al. J.A.M.A., 1997, 277: 231-237). While GWS patients do not in general suffer from classic rheumatic diseases, the signs and symptoms are reminiscent of atypical connective tissue diseases such as fibromyalgia, chronic fatigue syndrome, and the process associated with exposure to silicone breast implants (SBI). Serological abnormalities including hypergammaglobulinemia and abnormal serum proteins have been reported in 45% of GWS patients (Grady, et al. Arch. Int. Med., 1998, 158: 367-371).
Hundreds of explanations for GWS have been proposed. In 1994, the U.S. Secretary of Defense and the Secretary of Veterans Affairs asked the Center for Disease Control and Prevention to conduct an official scientific study exploring possible causes of GWS. The study was aimed at organizing reported symptoms into a defined case, characterizing clinical features, and evaluating risk factors. The results are described by Fukuda, et al. J.A.M.A., 1998, 280: 981-988). Fukuda et al., assessed a population of Gulf War Veterans with respect to many of the proposed explanations for GWS. The study included assessment of physical symptoms; blood, urine, and stool analysis; and serological assays. Tests were conducted to detect the presence of various viruses, bacteria, mycoplasm, and parasites. Serum was tested for yellow fever, dengue, Sindbis, West Nile, and phlebotomus fever viruses (Naples and Sicilian); Toscana, Karimbad, and Isfahan viruses; Rickettsia typhi and Rickettsia rickettsii; Coxiellla burnetii; Ehrlichia chaffeensis; Leishmania tropica and Leishmania donovani; Toxoplasma gondii; Schistosoma mansoni and Schistosoma haematobium; Strongyloides stercoralis; Helibacter pylori; Clostridium botulinum; and Bacillus anthracis. Stool specimens were tested for red and white blood cells; ova and parasites of Cryptosporidium parvum, Cyclospora cayetanensis, Isospora belli, and microsporidia; enteroviruses; and bacteria strains of Salmonella, Shigella, Yersinia, Campylobacter, and Escherichia coli (0157:H7). While this study is considered an official and comprehensive report on GWS, no attempt was made to assess alternative explanations, such as adjuvant's disease.
The Persian Gulf Veterans Coordinating Board has addressed the possibility of exposures to chemical and biological agents. The Board, however, attempted to account for these illnesses without defining a molecular pathology (Persian Gulf Veterans Coordinating Board. Arch. Int. Med., 1995, 155: 262-268).
One theory posits that GWS results from a dysregulation of the immune system (Hyams, et al. Ann. Int. Med., 1996, 125: 398-405). The GWS patients suffer from various symptoms similar to those having autoimmune diseases, but cannot be diagnosed with a “classic” rheumatic disease. Gulf War veterans and attendant civilian personnel received a variety of immunizations in preparation for possible deployment to the Persian Gulf theater (David, et al. Br. Med. 1997, 314: 239-240). It has been suggested that GWS may result from an imbalance in the immune system. It was hypothesized that the imbalance may be due to an adverse reaction to a vaccination. It was noted in some patients that the onset of illness occurred within weeks of receiving a full complement of immunizations. These individuals displayed symptoms of GWS soon after vaccination and were not deployed. Other individuals were deployed, but returned home before the start of the war because of severe joint and muscle pain, as well as neurological problems. Additional personnel from the Gulf War became ill years later. These individuals, however, report the same symptoms as those who became ill only weeks after their vaccinations. The variability in the onset of disease symptoms, as well as differences in their severity, may be due to individual immune responses. Such variability is reportedly regulated at a genetic level involving the histocompatibility complex (Madzhidov, et al. Biull. Eksp. Biol. Med., 1986, 102: 74-76; Lorentzen, et al. Transplant. Proc., 1995, 27:1532-1534,).
A possibility exists that the immunizations administered to all personnel involved in the Gulf War may be linked to the etiology of GWS. The immunizations administered typically comprised an antigen and an immunological adjuvant. The adjuvants function to boost the protective effect of the immunization by eliciting a stronger immune response against the antigen. The adjuvants are capable of stimulating the immune system's cell-mediated and humoral responses against the antigen being administered. Cases have been reported, however, where the adjuvants cause a more generalized and indiscriminate stimulation of the immune system. This can disrupt the balance of self-regulatory mechanisms within the immune system and lead to autoimmune disease (Kleinau, et al. Scand. J. Rheumatol. 1995, 101: 179-181; Madzhidov, et al. Biull. Eksp. Biol. Med. 1986, 102: 74-76; Lorentzen, et al. Transplant. Proc. 1995, 27: 1532-1534).
Fibromyalgia, chronic fatigue syndrome, and the symptoms associated with exposure to silicone breast implants, have been correlated with the presence of anti-polymer antibodies (APA), particularly antibodies to polyacrylamide, in the blood of individuals suffering from these conditions (see, e.g., U.S. Pat. No. 5,834,215 to Garry et al., Edlavitch, Lancet, 1997, 349: 1170; De Jong et al., Clin. Exp. Rheumatol., 2002, 20:151-160; and Bazzichi et al., Arthritis Res. Ther., 2007, 9(5), online article available at the website arthritis-research(dot)com/content/9/5/R86).
There is an ongoing need to identify markers, such as antibodies, for diseases and conditions with unknown or unclear etiology. The methods and kits described herein address this need.